The Institute of Medicine report, Ending Neglect: The Elimination of Tuberculosis in the United States, calls for the development of better tools for accurately identifying latently infected individuals. In countries such as the United States, where the incidence of latent tuberculosis is relatively low, the specificity of the current tuberculin skin test is too low to yield a high positive power of prediction. The goal of the proposed research is proof of concept for a diagnostic test of very high specificity, based upon the ultra sensitive detection of a Mycobacterium tuberculosis (Mtb) protein in peripheral blood. The specific aims are: to develop a bead capture ELISA sensitive enough to detect the Mtb homolog of alpha-crystallin at a low picomolar concentration, and to demonstrate that this protein can be detected in sera from Mtb - infected subjects. If this very specific and sensitive diagnostic test can be developed and commercialized, it could be used to guide prophylactic treatment recommendations for individuals latently infected with Mtb. Such a test has been identified as a high priority goal to facilitate a National plan to eliminate tuberculosis in the United States.